Over 43 million Americans smoke. Smoking is responsible for 443,000 deaths costing the US $96 billion in health care annually. NicVAX is an innovative nicotine vaccine to help smokers quit and, unlike current therapies, remain abstinent while reducing craving and withdrawal symptoms. Its unique immunological mechanism of action elicits the production of anti-nicotine antibodies that last for several months and sequester nicotine in the blood preventing it from reaching nicotinic receptors in the brain. Since it does not act centrally, NicVAX is safe with no CNS side effects. A Phase IIb "proof-of-concept" clinical trial for NicVAX demonstrated statistically significant rates of smoking cessation and continuous long-term smoking abstinence for subjects with high levels of anti- nicotine antibodies elicited by NicVAX. Recently, Nabi and the U.S. Food and Drug Administration (FDA) agreed on the design and protocols of two pivotal Phase III clinical trials for NicVAX under the Special Protocol Assessment (SPA) procedure. The SPA forms the foundation to support approval of a New Drug Application, or NDA. All components for a successful clinical trial have been implemented. Twenty-two investigative sites have been selected, and include highly-experienced academic-based smoking cessation centers and experienced non-academic sites. These include all 9 sites that previously participated in the NicVAX phase IIb study. Nabi is seeking partnership with NIDA/NIH under the 2009 Recovery Act GO Grant awards to support further development of the vaccine specifically the first of one of two Phase III trials required by the FDA for product licensure: "Phase III, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Assess Efficacy, Immunogenicity and Safety of 3'-aminomethylnicotine-P. aeruginosa r-Exoprotein A Conjugate Vaccine (NicVAX) as an Aid to Smoking Cessation". The study will enroll 1000 subjects who want to quit smoking will be randomized to one of two treatment groups: (1) placebo control;or (2) 400 <g of NicVAX. Final data will be available within 2- years of initiation of the study. Support from the Recovery Act will enable Nabi to continue expediting the development of NicVAX beyond this grant. We believe that NicVAX, the first of its kind nicotine vaccine, will have a significant positive impact on the health care system in the US as well as the large number of morbidity and mortality cases associated with smoking. PUBLIC HEALTH RELEVANCE: Smoking is responsible for 443,000 deaths costing the US $96 billion in health care annually. NicVAX is an innovative nicotine vaccine to help smokers quit and, unlike current therapies, remain abstinent while reducing craving and withdrawal symptoms. Its unique immunological mechanism of action elicits the production of anti-nicotine antibodies that last for several months and sequester nicotine in the blood preventing it from reaching nicotinic receptors in the brain. Since it does not act centrally, NicVAX has a favorable safety profile with no CNS side effects. We believe that NicVAX, the first of its kind nicotine vaccine, will have a significant positive impact on the health care system in the US as well as the large number of morbidity and mortality cases associated with smoking.